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Sepsi

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Sepsi

  1. 1. SEPSI
  2. 2. Definita come “la risposta sistemica dell’ospite all’infezione da parte di microrganismi o alle loro tossine” Spazia dalla risposta infiammatoria sistemica alla disfunzione d’organo all'insufficienza di multi-organo
  3. 3. INFEZIONE Evento legato all’ingresso e alla colonizzazione di tessuti o della superficie corporea dell’ospite normalmente sterili da parte di microorganismi. La risposta infiammatoria che ne consegue realizza una condizione di malattia localizzata o sistemica con danno cellulare o tissutale .
  4. 4. BATTERIEMIA Presenza di batteri nel sangue documentati da emocolture positive non sempre accompagnata da manifestazioni di interessamento sistemico. Transitoria. Autolimitante.
  5. 5. Quando la causa è di origine infettiva si parla di sepsi
  6. 6. SEPSI E’ una risposta infiammatoria sistemica che riconosce un’eziologia infettiva. Le manifestazioni cliniche della sepsi sono le stesse della SIRS. La identificazione di una sepsi prevede il riconoscimento di un nesso causale diretto fra le manifestazioni sistemiche ed il processo infettivo .
  7. 7. <ul><li>Fattori associati alla aumentata incidenza dei casi di sepsi e di shock settico </li></ul><ul><li>Maggiore consapevolezza e sensibilità nella diagnosi </li></ul><ul><li>Aumento del numero dei pazienti immunocompromessi </li></ul><ul><ul><ul><ul><li>Utilizzo di farmaci citotossici e/o immunosopressivi </li></ul></ul></ul></ul><ul><ul><ul><ul><li>AIDS </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Alcolismo </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Malattie neoplastiche </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Diabete mellito </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Pazienti trapiantati </li></ul></ul></ul></ul><ul><li>Uso indescriminato di antibiotici che creano il fenomeno della multiresistenza </li></ul><ul><li>Prolungamento della vita media </li></ul><ul><li>Maggiore utilizzo di procedure invasive diagnostiche/terapeutiche (CVC,catet vescicale, protesi chirurgiche, apparecchi per inalazione, sondino naso-gastrico, nutrizione enterale) </li></ul>
  8. 9. Sorgenti di sepsi   polmone addome pelle Appar urinario SNC Maggiori patogeni acquisiti in comunità S.pneumoniae H. influenzae Legionella sp. Chlamydia pneumoniae E. Coli Bact. fragilis S. pyogenes S. aureus Clostridium sp. Polymicrobial infections Aerobic gram - bacilli P. aeruginosa Staphylococcus sp. E. Coli Klebsiella sp. Enterobacter sp. Proteus sp. S.pneumon. N.meningit. Lis monoc E Coli H influenzae Maggiori patogeni nosocomiali Aerobic gram negative bacilli Aerobic gram negative bacilli Anaerobes Candida sp. Staphylococcus aureus Aerobic gram negative bacilli Aerobic gram negative bacilli Enterococcus sp. P.Aeruginos E coli Klebsiella sp. Staphylococcus sp.
  9. 10. Condizioni cliniche predisponenti Agenti etiologici Granulocitopenia <ul><li>Bacilli enterici Gram -, Pseudomonas </li></ul><ul><li>Aspergillus, Mucorales </li></ul>Deficit immunita’ cell-mediata Terapia corticosteroidea <ul><li>Listeria monocytogenes </li></ul><ul><li>Salmonella, Micobatteri </li></ul><ul><li>HSV, VZV,CMV </li></ul>Asplenia <ul><li>Streptococcus pneumoniae </li></ul><ul><li>Haemophilus influenzae </li></ul><ul><li>Neisseria Meningitidis </li></ul>Cirrosi epatica <ul><li>Vibrio, Yersinia, Salmonella </li></ul><ul><li>Bacilli enteroco gram neg </li></ul><ul><li>Streptococcus pneumoniae </li></ul><ul><li>Haemophilus influenzae </li></ul>Diabete mellito <ul><li>Pseudomonas, E. Coli </li></ul><ul><li>Mucorales </li></ul>
  10. 11. Fisiopatologia Componenti microbiche (LPS, peptidoglicano, mannano etc) TNF α IL-1 IL-2 PAF Liberazione di IL-2 INF γ e GM-CSF dai linf T Liberazione di tromb A2, prostaglandine e leucotrieni Attivazione e aggregazione PLT Attivazione fattori coagulazione e complemento Attivazione e degranulazione neutrof liberazione radicali O2 e proteasi Danno endoteliale SEPSI Sindrome settica SHOCK Settico Risposta infiammatoria sistemica Danno tessutale persistente Danno tessutale persistente ad almeno un sito + ipertensione refrattaria
  11. 12. Sepsis: Defining a Disease Continuum <ul><li>A clinical response arising from a nonspecific insult, including  2 of the following: </li></ul><ul><ul><li>Temperature  38 o C or  36 o C </li></ul></ul><ul><ul><li>HR  90 beats/min </li></ul></ul><ul><ul><li>Respirations  20/min </li></ul></ul><ul><ul><li>WBC count  12,000/mm 3 or  4,000/mm 3 or >10% immature neutrophils </li></ul></ul>SIRS = Systemic Inflammatory Response Syndrome SIRS with a presumed or confirmed infectious process Sepsis SIRS Infection/ Trauma Severe Sepsis Adapted from: Bone RC, et al. Chest 1992; 101:1644 Opal SM, et al. Crit Care Med 2000; 28:S81
  12. 13. Relationship Of Infection, SIRS, Sepsis Severe Sepsis and Septic Shock Bone et al. Chest 1992; 101:1644 SIRS INFECTION PANCREATITIS BURNS TRAUMA OTHER SEPSIS SEVERE SEPSIS SEPTIC SHOCK
  13. 14. Sintomi <ul><li>Esordi improvviso </li></ul><ul><li>Febbre preceduta da brivido irregolare intermittente </li></ul><ul><li>Brusche elevazioni termiche con brivido nella stessa giornata </li></ul><ul><li>Nei soggetti defedati: ipotermia </li></ul><ul><li>Tachipnea e tachicardia </li></ul>
  14. 15. Sindrome settica <ul><li>Sepsi associata a uno o più segni di disfunzione d’organo dovuti ad ipoperfusione/ipossia tissutale: </li></ul><ul><li>Acidosi lattica </li></ul><ul><li>Alterazione dello stato mentale </li></ul><ul><li>Oliguria (< 0.5 ml/h, senza terapia per 1 h </li></ul><ul><li>almeno) </li></ul><ul><li>Ipossia </li></ul>
  15. 16. Nella sindrome settica…… <ul><li>Inadeguata perfusione tissutale : </li></ul><ul><li>Oliguria </li></ul><ul><li>Ipossiemia </li></ul><ul><li>Aumento lattacidemia </li></ul><ul><li>Alterazione condizioni psichiche (adinamia, delirio) </li></ul><ul><li>Apparato digerente: anoressia, nausea, vomito, disturbi dell’alvo, epatosplenomegalia </li></ul><ul><li>Cute: petecchie ed ecchimosi </li></ul><ul><li>cellulite eruzioni maculopapulose </li></ul><ul><li>eczema grangrenoso </li></ul>SEPSI MENINGOCOCCICA GRAM + Pseudomonas Aeruginosa Gram -, miceti
  16. 17. Complicanze <ul><li>Insufficienza renale </li></ul><ul><li>Insufficienza cardiaca </li></ul><ul><li>Ittero (epatocellulare o emolitico) </li></ul><ul><li>Manifestazioni emorragiche: </li></ul><ul><li>CID: coagulazione intravascolare disseminata </li></ul><ul><li>Apoplessia surrenalica o S.di Waterhouse-Friderichsen </li></ul>
  17. 18. Sepsis: Defining a Disease Continuum Bone et al. Chest 1992;101:1644; Wheeler and Bernard. N Engl J Med 1999;340:207 Sepsis SIRS Infection/ Trauma Severe Sepsis <ul><li>Sepsis with  1 sign of organ failure </li></ul><ul><ul><li>Cardiovascular (refractory hypotension) </li></ul></ul><ul><ul><li>Renal </li></ul></ul><ul><ul><li>Respiratory </li></ul></ul><ul><ul><li>Hepatic </li></ul></ul><ul><ul><li>Hematologic </li></ul></ul><ul><ul><li>CNS </li></ul></ul><ul><ul><li>Metabolic acidosis </li></ul></ul>Shock
  18. 19. SHOCK SETTICO Ulteriore progressione della sindrome settica in cui oltre alla disfunzione d'organo, che a questo punto diventa pluriorganica, si associa instabilità di circolo con ipotensione ( PA < 90 mm Hg nei soggetti normali e PA< 40 mm Hg rispetto ai valori basali nei soggetti ipertesi). L'ipotensione può rispondere alla somministrazione di liquidi e amine. Nei casi più gravi non vi è più risposta si parla allora di SHOCK SETTICO IRREVERSIBILE
  19. 20. Mortality Increases in Septic Shock Patients Mortality Incidence Balk, R.A. Crit Care Clin 2000;337:52 Approximately 200,000 patients including 70,000 Medicare patients have septic shock annually Septic Shock 53-63% 20-53% Severe Sepsis 300,000 7-17% Sepsis 400,000
  20. 21. MOF/MODS Multi organ failure/multi organ disfunction syndrome Presenza in pazienti con malattia acuta di disfunzione multiorgano tale da determinare l’ incapacità a mantenere l’omeostasi senza interventi correttivi
  21. 22. <ul><li>Multiple disfunzioni d’ organo </li></ul><ul><li>Apparato respiratorio : </li></ul><ul><li>ARDS (sindrome da difficolta’ respiratoria acuta) </li></ul>Edema polmonare non cardiogeno
  22. 23. <ul><li>Apparato digerente: </li></ul><ul><li>Fenomeni emorragici= gastrite erosiva acuta </li></ul><ul><li>Disturbi funzionali= ileo paralitico </li></ul><ul><li>Disfunzioni epatiche= ittero, ipoglicemia </li></ul><ul><li>Reni: insufficienza renale acuta </li></ul><ul><li>Lesionin glomerulari </li></ul><ul><li>Lesioni tubulo-interstiziali </li></ul><ul><li>Necrosi tubulare </li></ul>
  23. 24. SNC: <ul><li>disorientamento </li></ul><ul><li>irritabilita’ </li></ul><ul><li>sopore .. . . . . coma franco </li></ul>Apparato emopoietico: <ul><li>Manifestazioni emorragiche </li></ul><ul><li>CID: coagulazione intravascolare disseminata </li></ul>Consumo di piastrine e fattori della coagulazione
  24. 25. DIAGNOSI <ul><li>Sintomatologia clinica: accessi febbrili preceduti da brividi, riscontro di una porta d’ingresso </li></ul><ul><li>Tachicardia > 90 bm’ </li></ul><ul><li>Tachipnea > 20 atti/min </li></ul><ul><li>Emocolture……… </li></ul>
  25. 26. Emocolture <ul><li>Prima della terapia antibiotica </li></ul><ul><li>In presenza di brivido e/o febbre elevata </li></ul><ul><li>Piu’ volte nel corso della giornata </li></ul><ul><li>3 emocolture= risposta positiva nel 99% dei </li></ul><ul><li>casi </li></ul>
  26. 27. <ul><li>Poich é la conferma batterioogica richiede alcuni giorni . . . . </li></ul><ul><li>iniziare la terapia in base ai soli </li></ul><ul><li>elementi clinici </li></ul>
  27. 28. Terapia antimicrobica empirica <ul><li>NEONATI </li></ul><ul><li>Sepsi ad insorgenza precoce (et à <1 settimana) </li></ul><ul><li>Sepsi ad insorgenza tardiva (età 1-4 settimane) </li></ul>Ampicillina+cefotaxima o ceftriaxone o Amminoglucoside (gentamicina, tobramicina) Ampicillina+cefotaxima o ceftriaxone o Amminoglucoside (gentamicina, tobramicina) Se S. Aureus: + oxacillina o vancomicina o teicoplanina
  28. 29. <ul><li>ADULTI </li></ul><ul><li>INFEZIONI CONTRATTE IN COMUNITA’, PZ NON NEUTOPENICO (NEUT >1000/ μ L) </li></ul><ul><li>Sepsi a partenza dalle vie urinarie </li></ul><ul><li>Sepsi secondarie ad infezioni cutanee </li></ul>Cefalosporina di III generazione o piperacillina o mezlocillina o aztreonam o imipenem o meropenem o Ticarcillina-acido clavulanico o Fluorochinolonico (e.v.) ± aminoglicoside Oxacillina o vancomicina o teicoplanina
  29. 30. <ul><li>Sepsi secondarie ad infezioni intestinali </li></ul>Cefalosporina di III generazione + metronidazolo oppure Imipenem o meropenem o clindamicina + aminoglicoside oppure aztreonam + metronidazolo o imipenem o meropenem o ticarcillina-acido clavulanico o piperacillina-tazobactam
  30. 31. <ul><li>ADULTI </li></ul><ul><li>b) SEPSI NOSOCOMIALI </li></ul><ul><li>Pz neutropenico (neut < 1000/ μ L) </li></ul>Ceftazidima o cefoperazone+ metronidazolo ± Aminoglicoside oppure Ticarcillina-acido clavulanico o piperacillina- tazobactam + Aminoglicoside oppure Imipenem o meropenem ± aminoglicoside
  31. 32. <ul><li>Pz non neutropenico (neut >1000/ μ L) </li></ul><ul><li>Pz tossicodipendente </li></ul><ul><li>Pz splenectomizzato </li></ul>Cefalosporina di III generazione + metronidazolo o ticarcillina-acido clavulanico o ampicillina –sulbactam o Imipenem o meropenem + aminoglicoside Oxacillina o vancomicina o teicoplanina + aminoglicoside Cefotaxima o ceftriaxone
  32. 33. Attualità in tema di terapia antibiotica per batteri meticillino-resistenti (Cocchi Gram + ) <ul><li>Quinopristin/Dalfopristin (Synercid) </li></ul><ul><li>Streptogramina iniettabile </li></ul><ul><li>Linezolid (Zyvoxid) </li></ul><ul><li>Oxazolidone, blocca la subunità 70S </li></ul><ul><li>Daptomicina (Cubicin) </li></ul><ul><li>Lipopeptide ciclico; si lega alla membrana cellulare, formando strutture di trasporto ionico </li></ul><ul><li>Oritavancina (Ly333328) </li></ul><ul><li>Glicopeptide </li></ul><ul><li>Dalbavancina (B-397) e </li></ul><ul><li>Telavancina (TD-6424) </li></ul><ul><li>Glicopeptidi semisintetici </li></ul>
  33. 34. Attualità in tema di terapia antibiotica batteri meticillino-resistenti (Cocchi Gram - ) <ul><li>Meropemen </li></ul><ul><li>Carbapenemico, già in commercio da alcuni anni </li></ul><ul><li>Aminoglicoside </li></ul><ul><li>Colistina </li></ul><ul><li>farmaco molto vecchio, ma molto efficace sugli Acinetobacter e Pseudomonas </li></ul>

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